[On inactivation of MHV-3 hepatitis virus by intestinal tissue of mice treated with prednisolone].
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Biomedical subjects
Publications and source records attributed to F Piccinino.
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Two hundred and four patients with biopsy-proven HBsAg-positive chronic active hepatitis were treated for at least 2 years with azathioprine, prednisolone or a combination of both, or were untreated. Prevalences of HBeAg, anti-HBe, and anti-HBc were 26, 58, and 100%, respectively. Criteria for improvement or progression of disease were based on clinical, biochemical, and morphologic parameters. Prednisolone therapy and combination therapy did not modify the course of the disease in HBeAg-positive patients; azathioprine therapy may have been deleterious for these patients. Among HBeAg-negative patients, deterioration or death occurred more frequently in those who were untreated than in those who received the combination of azathioprine and prednisolone. Prednisolone therapy was of moderate effect, whereas azathioprine did not influence the outcome.
A patient with HBsAg-positive subacute hepatitis who presented a progressively deteriorating clinical condition was treated with azathioprine (100 mg/day) for eight months. Although the clinical symptoms disappeared and the biochemical abnormalities decreased, the disease nevertheless progressed to chronic active hepatitis. Moreover, azathioprine favoured hepatitis B virus replication since titers of HBsAg, HBeAg and Dane-particle-associated core-antigen, as detected by radioimmunoassay, increased during treatment. In all, this drug was only of moderate use to our patient.
To test the hypothesis that households of anti-HCV positive subjects might be at increased risk of HCV infection, a case-control study was carried out comparing 518 family members of 205 anti-HCV positive subjects (index carriers) with 281 family members of 100 anti-HCV negative subjects (index controls), consecutively observed in ten gastroenterology units in different Italian regions. The index carriers were age and sex matched to the index controls and their households were similar with respect to the main sociodemographic characteristics. Anti-HCV antibodies were found in 6.9% (36/518) of household members of index carriers and in 3.2% (9/281) of household members of index controls (p < 0.05). The results of multiple logistic regression analysis showed that being over 50 years of age was the sole independent predictor for a household contact of the likelihood of being anti-HCV positive (O.R. 3.6; C.I. 95% = 1.5-8.2). Being in the household of an anti-HCV index carrier was marginally associated to anti-HCV positivity (O.R. 2.0; C.I. 95% = 0.9-4.6). No association was found for sex, area of residence, family size, lowest level of schooling, or any type of family relationship. These findings are not in compliance with the statement that household contacts of HCV carriers are at increased risk of HCV infection. The 3.2% anti-HCV prevalence rate observed among household contacts of anti-HCV negative index controls may suggest that the true anti-HCV prevalence in the general population in Italy is nearly 2.5 times as high as the 1.3% found in Italian blood donors.
204 patients with biopsy-proven CAH were observed for at least one year with periodic examinations including a second liver biopsy for each patient. Patients were assigned at random to a group left untreated or treated with either azathioprine 100 mg daily, or prednisolone (Dutimelan 8 15), or prednisolone plus azathioprine 50 mg daily. The outcome, assessed on clinical, biochemical and histological parameters, was correlated to the presence or absence of HBeAg and its antibody. No treatment was effective in HBeAg-positive patients whereas, among anti-HBe-positive patients, those who were treated with the association of steroids and azathioprine more frequently showed improvement and less frequently deteriorated (p less than 0.01) than untreated patients. Thus, HBsAg/anti-HBe-positive patients with CAH may be treated with the combination of these drugs, even though many side-effects may occur and there are frequent relapses after discontinuation of treatment.
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In 1983, a pilot project of universal hepatitis B vaccination was introduced in a hyperendemic area in southern Italy (Afragola) and is ongoing to date. In this area before the start of vaccination, we found significant evidence of HBV endemicity: the acute viral hepatitis B incidence in the general population averaged 63/100,000; the HBsAg and anti-HBc prevalence rates were 13.4% and 66.9%, respectively; there was involvement of hepatitis B virus (HBV) in 48.1% of chronic liver pathologies (46.3%) in chronic viral hepatitis, 49.5% in cirrhosis and 71.7% in hepatocellular carcinoma cases). We studied the acute viral hepatitis incidence during the vaccination period from 1983 to 1997 and compared the HBsAg and anti-HBc prevalences in 1978 to those in 1997, after 15 years of vaccination. The HBV-related chronic pathology prevalence was also studied. We found a remarkable drop in the acute viral hepatitis incidence, from an average annually of 63/100,000 in the five years before vaccination to 3/100,000 in the last five years of vaccination. In addition, the HBsAg carrier prevalence in the general population decreased from 13.4% in 1978 to 3.7% in 1997. The percentage dropped in children and adolescents from 6.8% to 0.7%, in young people from 10.2% to 1.1% and in adults from 15.8% to 4.0%. The anti-HBc carrier prevalence, found to be 66.9% in 1978, was 34.2% in 1997. Finally, we found a much less significant involvement of HBV in chronic liver pathologies; in fact, it was present in only 18.2% of cases in 1997 and in 48.2% in 1982. In the light of the data, we can assert that universal hepatitis B vaccination has had a substantial effect on HBV endemicity in the Afragola area. We believe that the reduction found in the incidence of acute viral hepatitis B and HBV-related chronic liver pathologies is connected to the decrease in HBV carriers in the area, which therefore reduces the risk of contagion for the unvaccinated.
The aims of the study were to evaluate the long-term efficacy and tolerability of different doses of interferon-alpha (IFN alpha) and different durations of treatment in chronic hepatitis C by comparing 3 or 6 mega units (MUs) three times weekly given for either 12 or 24 months, and the possibility of obtaining a response in non-responder patients by increasing the dose or by administering IFN daily. A total of 504 patients with non-cirrhotic chronic hepatitis C enrolled in a multicentre study were consecutively assigned to receive either 3 (255 patients) or 6 MU (249 patients) of lymphoblastoid IFN alpha 3 times a week (tiw). At the 12th month of therapy, patients with normal aminotransferase (AMT) in both groups were either given IFN for an additional 12 months with an unmodified or halved dose, or else discontinued therapy. For patients with unmodified AMT levels after 6 months of therapy, the IFN dose was doubled in the 3-MU group, while it was administered at 3 MU daily in the 6-MU group. When no improvement was achieved, therapy was discontinued; otherwise it was prolonged until the 18th month. Patients were followed up for 12 months after discontinuing IFN. Of the 255 patients enrolled at 3 MU, therapy was stopped during the first 6 months in 36 patients (14.1%) because of side effects, and in 24 (9.4%) because of lack of cooperation. Of the remaining 195 patients at the 6th month of therapy, 119 (61%) had normal and 76 (39%) unmodified AMT levels; 14 of the 76 normalized AMT after doubling the dose of IFN, but only 5 (6.6%) had a sustained response. Of the 119 patients with normal AMT, 40 discontinued IFN at the 12th month (schedule A), 39 remained at 3 MU tiw (schedule B) and 40 were given a dose of 1.5 MU tiw (schedule C) for an additional 12 months. At the end of follow-up, 23/40 (57.5%) patients in schedule A, 31/39 (79.5%) on schedule B and 29/40 (72.5%) on schedule C still had normal AMT (A vs. B p = 0.04). In an intention-to-treat analysis, the sustained response rate for patients enrolled at 3 MUs, including the 5 initial non-responders, was 34.5%. Of the 249 patients enrolled at 6 MU, therapy was discontinued during the first 6 months for 39 (15.7%) because of side effects, and for 27 (10.8%) because of lack of cooperation. Of the remaining 183 patients at the 6th month of therapy, 110 (60%) had normal and 73 (40%) unmodified AMT levels. Of the 73 patients, 55 accepted the daily regimen and 8 of them (14.5%) showed a sustained response. Of the 110 patients with normal AMT, 32 (29.1%), despite normalization of AMT, spontaneously discontinued IFN or reduced the dose because of a poor quality of life, while 78 continued with 6 MU until the 12th month, when therapy was discontinued for 28 (schedule A1); 24 patients were given an unmodified dose (schedule B1) and 26 a halved dose (schedule C1) for an additional 12 months. At the end of follow-up, 18/28 (64.3%) patients on schedule A1, 19/24 (79.2%) on schedule B1 and 19/26 (73.1%) on C1 still had normal AMT (p = NS). In an intention-to-treat evaluation, the sustained response rate for patients enrolled at 6 MU, including the 8 from the daily treatment, was 25.7% (64/249). HCV viraemia was undetectable 1 year after discontinuation of IFN in 72.6% of patients with a sustained response. Sustained response was observed in 36.4% of patients with minimal, 46.6% of those with mild, and 33.3% with moderate or severe histological activity (p = NS). The rate of sustained response was lower in patients with genotype 1b (23.6%) than in those with genotype 2a (67.8%, p = 0.002) or genotype 3 (50%, p = 0.03), irrespective of the histological activity. In conclusion, 6 MU IFN alpha are no more effective than 3 MU in inducing a sustained response in treatments of both 12 and 24 months. A 24-month treatment is more effective than a 12-month treatment in maintaining a biochemical response after discontinuation of IFN. In terms of efficacy, compliance and cost, 3 MU for 24 months app
We analyzed retrospectively the effect of immunosuppressive therapy in 139 children with HBsAG-positive chronic active hepatitis (CAH) observed in four liver units in Italy from 1974 to 1982. All children had been observed for at least 12 months. Of these 139 patients, 38 were treated with steroids (prednisolone or prednisone from 1 to 2 mg/kg daily), 78 with combination therapy (prednisolone or prednisone 1 mg/kg daily in combination with azathioprine, 2 mg/kg daily) and 23 were not treated. The outcome of the disease was assessed by evaluating clinical, biochemical, and histological parameters on the basis of preselected criteria. Untreated patients deteriorated more frequently than those treated with steroids (34.8% versus 13.2%, p less than 0.05) or those receiving combination therapy (34.8% versus 10.3%, p less than 0.01). Remission or improvement was observed more frequently in steroid-treated and combination-treated patients than in the untreated ones (p less than 0.001 and p less than 0.01, respectively). At the end of the study, only one untreated patient had died of liver failure. Remission was observed in about 10% of patients in the two groups of treatment, but in the untreated one, this event never occurred. Although this study is retrospective and presents some shortcomings, the data clearly indicate that steroid and combination therapy are not deleterious, and are possibly helpful, to children with HBsAg-positive CAH.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to evaluate the spread of viral hepatitis to dialysis patients and staff, 83 out of the 134 dialysis units operating in Italy at present were surveyed. The results were statistically evaluated. Of the 81 Italian centres surveyed, 66 were affected by viral hepatitis. There were 450 cases of infection among patients on regular dialysis treatment (9.7% of all dialysed patients). Of these 450, 163 had icteric viral hepatitis (116 HBsAg positive), 145 has non icteric hepatitis (100 HBsAg positive) and 142 were HBsAg carriers. The mortality rate among the dialysis patients with hepatitis was 9.1% with death occurring most frequently in icteric cases. Of the 133 cases of viral hepatitis observed among medical and nursing staff, 103 of these were HBsAg positive. Moreover, there was a higher risk of hepatitis infection observed in patients on regular dialysis treatment by multi-patient central system plate dialysers, in carriers of exteriorized arteriovenus shunt in patients who were submitted to frequent dialysis sessions and haemotransfusions.
To obtain data on the clinical presentation and the course of the disease of biopsy-proven chronic persistent hepatitis (CPH), we coordinated a multicentre retrospective study on 1197 patients observed in 16 liver units throughout Italy from 1975 to 1985. Most patients were asymptomatic and CPH was often diagnosed either after a chance finding of liver enlargement, or increased serum aminotransferases and/or HBsAg antigenemia. Of the 1197 patients, 534 (44.6%) were HBsAg-positive and 663 (55.4%) were HBsAg-negative. HBeAg was tested in 356 of the 534 positive cases and detected in 58.4% of them. This percentage was higher (80%) in patients under 20. Hepatitis delta virus infection (HD-Ag in liver tissue and/or anti-HD in serum) was detected in 28 (14.7%) of the 191 patients tested on presentation. Liver function tests showed mild hepatic involvement in both HBsAg-positive and negative cases, a pronounced derangement being observed only in patients with HDV infection. A second liver biopsy was performed in 212 patients (144 HBsAg positive and 68 HBsAg negative) and the outcome of the disease was evaluated only in these 212 patients. Of the 144 HBsAg-positive cases followed-up from one to ten years (median 4 years), 47 recovered, 70 remained unchanged and 27 developed chronic active hepatitis or cirrhosis. Clearance of HBsAg was uncommon even in patients who recovered. Being under 15 years of age favourably affected the course of the disease, while HDV infection was correlated to an unfavourable outcome. Among those patients who were HBeAg positive on presentation and who underwent a second affect the outcome. Of the 68 HBsAg-negative clearly affect the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
Eighty-eight drug addicts from the "BAN Center" in Torre Annunziata (Naples) and 88 normal subjects pair-matched for age and sex were tested for IgG to human immunodeficiency virus (HIV), herpes simplex virus (HSV) type 1 and 2 and cytomegalovirus (CMV). A high prevalence of subjects with antibodies to HSV-1 and CMV (80.7% and 65.9%) were recorded in the control group testifying to the high level of these infections in Campania. Prevalences were higher in drug addicts, and drug abuse was identified as a risk factor for the acquisition of CMV infection (odds ratio = 2.3). Moreover, drug addiction is also a risk factor for HSV-2 and HIV infection as demonstrated by the observation that drug abusers were anti-HSV-2 (9.1 vs. 1.1%, odds ratio = 6.16) or anti-HIV (11.4 vs. 0%, odds ratio = 23.6) positive more frequently than normal controls. Thus, drug addiction is a risk factor for the acquisition of HIV, HSV-2 and CMV infections. This is probably due to similar habits, frequent among drug addicts from our geographic area and uncommon in the normal population, such as tattooing, needle-sharing needlestick and unsafe sex. Some of these habits, such as unsafe sex and tattooing, seem to be, per se, risk factors for the acquisition of both HIV and CMV infections. The data also suggest that HIV infection was probably introduced in Campania more recently than in northern and central Italy where the prevalence of anti-HIV positive cases among drug addicts is definitely higher.
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